Pharmaceuticals



United States Patent PHARMACEUTICALS Harland Edward Heilig, Highland Park, N.J., and Felix Anthony Jehle, Brooklyn, N.Y., assignors to Olin Mathieson Chemical Corporation, New York, N.Y., a corporation of Virginia No Drawing. Filed Sept. 4, 1958, Ser. No. 758,921

2 Claims. (Cl. 167-82) This invention relates to, and has for its object, the provision of an improved pharmaceutical tablet, and the method of preparing same.

Compressed tabletstbat contain a pharmacologically active material (therapeutic agent, medicament) which is hygroscopic or water-soluble, or which is decomposed or inactivated by water (hereinafter referred to as a watersensitive medicament) are prepared in such a way that the water-sensitive medicament, which is present in the center of the tablet (the core) is surrounded by a Waterproof film (moisture barrier film) which is applied to the compressed tablet prior to the coating thereof. The purpose of this film is to prevent the penetration (seepage) of moisture into the core where the moisture could decompose or inactivate the water-sensitive medicament contained therein thereby destroying its therapeutic effectiveness. The primary source of this moisture is the water-based coating syrups which are applied as aqueous solutions to the tablet to impart smoothness and esthetic appearance to the tablet. A natural consequence of such a water-proof film is the prolongation of the disintegration time of the tablet in the gastrointestinal tract, which is generally acceptable but not considered to be ideal inasmuch as the disintegration time of the film coating and consequently the core far exceeds the disintegration period and resultant time of release of the medicament which would give maximum beneficial results of the therapeutic agents being administered in the tablet.

Among the substances previously utilized to provide a water-proof (moisture barrier) film to the compressed tablet prior to coating were oils (e.g. peanut oil), alcoholic solutions of gums and resins (e.g. sandarac), higher fatty acids (e.g. myristic acid) and other film formers such as ethyl cellulose. Most commonly, an alcoholic solution of a pharmaceutical grade shellac was used as the Water-proofing agent, the shellac being applied in successive coats. The film formed by the shellac being hard, strong, and insoluble in both water and the dilute acids of the stomach tended to prevent the distintegration of the film in the stomach thereby delaying the release of the therapeutic materials for several hours or until the tablet reached the more alkaline portions of the jejunum.

It, therefore, is an object of this invention to provide a pharmaceutically acceptable liquid composition intended for use as a tablet core coating composition that is sufficiently impervious to water to act as a moisture barrier film but which disintegrates at an adequate rate in the stomach to permit release of the medicament therein.

It is a further object of this invention to provide tablets intended for oral administration containing a core which comprises a water-sensitive medicament and a coating thereof which essentially comprises shellac and polyvinylpyrrolidone.

A still further object of this invention is to provide a method of preparing a pharmaceutical tablet containing a core which comprises a water-sensitive medicament and a core coating which essentially comprises shellac and polyvinylpyrrolidone.

The objects of this invention can be achieved by coating a tablet core containing a water-sensitive medicament with a solution of shellac and polyvinylpyrrolidone in alcohol. The shellac and polyvinylpyrrolidone together represent about 24-44% (w./w.) of the coating solution, the shellac preferably being present in about 14% of the solution and the polyvinylpyrrolidone preferably being present in about 10-30% of the solution,-about 25% being preferred.

To prepare the tablets of this invention one or more water-sensitive medicaments are granulated in the usual manner either by themselves or with other therapeutically active ingredients and/or inactive excipients andcompressed into tablet cores in the manner well known in the art. Among suitable water-sensitive medicaments may be mentioned hygroscopic materials (e.g. potassium chloride and potassium iodide) antibiotics (e.g. penicillin, nystatin, and tetracycline), vitamins (e.g. ascorbic acid), various iron salts, effervescent salts, salicylate preparations (e.g. acetylsalicyclic acid) and numerous other active medicinal ingredients.

The core, thus formed is treated with a solution of shellac and polyvinylpyrrolidone (formed by dissolving the shellac in Warm alcohol and adding the polyvinylpyrrolidone), the shellac and polyvinylpyrrolidone preferably being present in the proportions indicated hereinbefore. This treatment is effected by applying the shellacpolyvinylpyrrolidone solution in successive applications to the tablet core utilizing the conventional methods of coating tablets.

The final tablet is then prepared by further coating with a water based coating syrup and if desired, color coatings can be applied until a tablet of desired size and color is obtained.

The following examples are illustrative, but by no means limitative, of the invention:

EXAMPLE I (a) Preparation of the coating composition Polyvinylpyrrolidone K30 (Antara Chemicals) gm 10 Shellac, Orange Flake (pharmaceutical grade,

arsenic free) em 14 Ethyl Alcohol SD-3A, q.s. ml

The shellac is dissolved in the alcohol which has been previously warmed to 50 C. When the shellac has been completely dissolved, the polyvinylpyrrolidone is added, with stirring, until it too has been completely dissolved.

(b) Preparation of the tablet core Grams Acetylsalicyclic acid r 975.0 Corn starch 85.0

Acacia 27.5

Talc 27.5

The above ingredients are placed in a mixing bowl and thoroughly mixed for 10 or 15 minutes. The mixture is then placed in a tablet machine and compressed. The compressed tablets are removed from the tablet machine, placed in a container and broken into coarse pieces. The broken tablet pieces are then screened to obtain uniform particles and placed in the tablet machine and again compressed.

(c) Coating the tablet core (d) Coating the tablet The dried and sifted shellac-polyvinylpyrrolidone coated tablets are returned to a coating pan and the pan is rotated. To the tumbling tablets, in the rotating coating pan, are added successive coats of an aqueous solufinishing coats of chocolate syrupare added and the tablets dried and polished to a high luster.

EXAMPLE II The procedure of Example I is repeated with the following coating composition substituted for that in step a of Example I:

Polyvinylpyrrolidone K30 (Antara Chemicals) 7 1 gm 30 Shellac, Orange Flake (pharmaceutical grade, ar-

senic free) gm 14 Ethyl Alcohol SD3A, q.s ml 100 EXAMPLE III The procedure of Example I is repeated with the following coating composition substituted for that in step a of Example I:

Polyvinylpyrrolidone K30 (Antara Chemicals) gm. 25 Shellac, Orange Flake (pharmaceutical grade, a

senic free) gm 14 Ethyl Alcohol SD-3A, q.s ml 100 The invention may be variously otherwise embodied within the scope of the appended claims.

What is claimed is:

1. A tablet intended for oral administration comprising a core containing a water-sensitive medicament and a coating thereof which essentially comprises shellac and polyvinylpyrrolidone in the proportion of about one part by weight of shellac to from about 0.7 to about 2.2 parts by weight of polyvinylpyrrolidone.

2. A multi-coated tablet intended for oral use comprising a core containing a Water-sensitive medicament, a film, of shellac and polyvinylpyrrolidone surrounding said core, and a coating of a water soluble material surrounding said film, said film comprising about one part by weight of shellac to from about 0.7 to about 2.2 parts by Weight of polyvinylpyrrolidone.

References Cited in the file of this patent UNITED STATES PATENTS 2,691,619 Bavley Oct. 12, 1954 2,820,741 Endicott Jan. 21, 1958 FOREIGN PATENTS 109,438 Australia Jan. 11, 1940 493,934 Great Britain Jan. 14, 1937 OTHER REFERENCES,

Schimmel Briegs, No. 233, August 1954.

Proceeding 40th Mid-year Meeting of Chem. Specialties Manuf. Assn, May 1954-, art. by Wilkinson et al., pp. 25-29. 

1. A TABLET INTENDED FOR ORAL ADMINISTRATION COMPRISING A CORE CONTAINING A WATER-SENSITIVE MEDICAMENT AND A COATING THEREOF WHICH ESSENTIALLY COMPRISES SHELLAC AND POLYVINYLPYRROLIDONE IN THE PROPORTION OF ABOUT ONE PART BY WEIGHT OF SHELLAC TO FROM ABOUT 0.7 TO ABOUT 2.2 PARTS BY WEIGHT OF POLYVINYLPYRROLIDONE. 